Here we propose a National Resouce for Translational and Developmental Proteomics (NRTDP). The science drivers are outlined in eight Driving Biomedical Projects that motivate the specific aims for four Technology Research and Development Projects. The impact of these combined activities, devoted to improving mass spectrometry-based proteomics using whole proteins as the primary unit of measurement, will be substantial. Integrated over all aspects of the resource (including biomedical application, technology development, dissemination and training), the projected impacts are aligned with both the spirit and the letter of a P41 Biomedical Technology Research Resource and the strategic goals of the NIH as a whole. Applying innovation to timely challenges in diverse areas of clinical and translational research will secure a leadership position for our nation in 'next-generation' proteomics technology. These technologies will serve driving projects and investigators to improve scientific understanding and diagnostics, ultimately improving the lives of cancer patients, recipients of kidney transplants, those afflicted with coronary heart disease, and to preserve fertility in women survivors of cancer (oncofertility). More specifically, we will focus ultra-high performance proteomics on sample sets deriving from research on various cancers, including chronic lymphocytic leukemia, multiple myeloma, and acute myeloid leukemia. In technology, we will accelerate the development of the leading platform for top-down proteomics, including two new Fourier-Transform instruments, new protein fractionation technologies, and the AUTOPILOT software suite to allow strategic objectives of biomedical projects to govern the most detailed aspects of data collection on a daily basis. A tailored workflow to enable pervasive and exhaustive analysis of core histones further augments the technology portfolio available in this deeply collaborative and deferential national resource housing a demonstrably high performing technical and administrative team. Good evidence of the team's ability to distill high-end research activities into robust servce lines is now visible. Interest in the laboratory as a hub for training has been robust (with over a dozen visiting scholars to date) and specific plans for expansion of these activities are included. Several routes of information and technology dissemeniation also described in the application. The administration and execution of all these activities is assured by a proven senior team operating the Proteomics Center of Excellence (PCE) at Northwestern, which also has very strong institutional backing to align proteomics ongoing in Chicago with national priorities of NIH-funded biological and translational research of the NIH. The advancement of general medical science envisioned here will be of interest to several institutes including NCI, NICHD, NIDDK, NIGMS, and NHLBI - all of which are heavily invested in proteomics research. Our team of senior researchers at the Proteomics Center of Excellence, along with over a dozen collaborating laboratories around the country, look forward to feedback regarding the proposed NRTDP.